Contribution Of left ventricular hypertrophy to symptoms and exercise intolerance in severe aortic stenosis

Background: Mechanisms governing symptoms and exercise intolerance in aortic stenosis (AS) are poorly understood. AS is characterised by left ventricular (LV) pressure overload leading to left ventricular hypertrophy, but the response is extremely variable. Our hypothesis was patients with high LV mass index (LVMI) would have more limitation before aortic valve replacement (AVR), and less improvement post-­‐AVR. Methods: Investigations were performed pre‐ and 6 months post‐AVR; transthoracic echocardiography (TTE): stenosis severity/diastolic function; cardiopulmonary exercise testing (CPEX): objective exercise capacity (peak VO2); cardiac magnetic resonance (CMR): LV mass/volumes, myocardial perfusion reserve (MPR), strain/strain rates – myocardial tissue tagging, myocardial fibrosis – late gadolinium enhancement (LGE). Repeatability of CPEX and CMR strain/strain rates was assessed. Matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) were measured pre­‐ and post‐AVR using biotinylated goat antibodies and immunoluminometric assays. Results: Forty‐six patients were studied pre‐AVR, 43 returned at 6 months. On multivariate stepwise regression analysis MPR was independently associated with age­‐ and sex‐corrected peak VO2 pre‐AVR (β=0.46, p=0.001). MPR was also inversely related to New York Heart Association functional class (p=0.001). LVMI and LGE were independently associated with MPR. Patients with high LVMI pre­‐AVR improved exercise capacity post­‐AVR (p=0.001). There was a corresponding improvement in MPR (p=0.03). MPR and LV end­‐diastolic volume at baseline predicted percentage change in peak VO2 on multivariate analysis (r2=0.29). Repeatability of peak VO2 and circumferential strain/strain rates was good. Reductions in MMP‐2 and TIMP‐2 post‐ AVR were significantly associated with fall in LV mass/volumes. Conclusions: Patients with high LVMI pre‐AVR did not have significant reduction in peak VO2. MPR was a novel independent association with peak VO2. LVMI and LGE were important associations with MPR. Contrary to our hypothesis those with high LVMI improved more post­‐AVR, with associated increased MPR. Further work is required to assess the prognostic importance of MPR in asymptomatic AS.